Immune cells defective for suv39h1

Abstract

The present invention relates to an engineered immune cell defective for Suv39h1. Preferably, said engineered immune cell further comprises a genetically engineered antigen receptor that specifically binds a target antigen. The present invention also relates to a method for obtaining a genetically engineered immune cell comprising a step consisting in inhibiting the expression and/or activity of Suv39h1 in the immune cell; and further optionally comprising a step consisting in introducing in the said immune cell a genetically engineered antigen receptor that specifically binds to a target antigen. The invention also encompasses said engineered immune cell for their use in adoptive therapy, notably for the treatment of cancer.

1 . An engineered immune cell, which is defective for Suv39h1. 
     
     
         2 . An engineered immune cell according to  claim 1 , which further comprises a genetically engineered antigen receptor that specifically binds a target antigen. 
     
     
         3 . The engineered immune cell according to  claim 1  or  2 , which is a T cell or an NK cell. 
     
     
         4 . The engineered immune cell of any one of  claims 1 to 3 , which is a CD4+ or CD8+ T cell. 
     
     
         5 . The engineered immune cell according to any one of  claims 1 to 4 , which is isolated from a subject. 
     
     
         6 . The engineered immune cell according to  claim 5 , wherein the subject is suffering from a cancer, or is at risk of suffering from a cancer. 
     
     
         7 . The engineered immune cell according to any one of  claims 1 to 6 , wherein the activity and/or expression of Suv39h1 in the said engineered immune cell is selectively inhibited or blocked. 
     
     
         8 . The engineered immune cell according to any one of  claims 1 to 7 , wherein said engineered immune cell expresses a Suv39h1 nucleic acid encoding a non-functional Suv39h1 protein. 
     
     
         9 . The engineered immune cell according to any one of  claims 2 to 8 , wherein the target antigen is expressed on cancer cells and/or is a universal tumor antigen. 
     
     
         10 . The engineered immune cell according to any one of  claims 2 to 9 , wherein the genetically engineered antigen receptor is a chimeric antigen receptor (CAR) comprising an extracellular antigen-recognition domain that specifically binds to the target antigen. 
     
     
         11 . The cell of any of  claims 2 to 10 , wherein the genetically engineered antigen receptor is a T cell receptor (TCR). 
     
     
         12 . A method of producing a genetically engineered immune cell comprising a step consisting in inhibiting the expression and/or activity of Suv39h1 in the immune cell; and further optionally comprising a step consisting in introducing in the said immune cell a genetically engineered antigen receptor that specifically binds to a target antigen. 
     
     
         13 . The method of  claim 12 , wherein the inhibition of Suv39h1 expression and/or activity comprises putting in contact the cell with at least an agent inhibiting the expression and/or activity of Suv39h1 and/or disrupting the Suv39h1 gene. 
     
     
         14 . The method of  claim 13 , wherein the agent is selected from small molecule inhibitors; antibodies derivatives, aptamers, nucleic acid molecules that block transcription or translation, or gene editing agents. 
     
     
         15 . An engineered immune cell, according to any one of  claims 1 to 11  or obtained according to the method of any one of  claims 12 to 14 , or a composition comprising said engineered immune cell, for use in adoptive cellular therapy of cancer.